POS1074 COMORBIDITIES AND EXTRA-ARTICULAR INVOLVEMENT IN PERSISTENT INFLAMMATORY AND NON-INFLAMMATORY DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS AND CONTROLS
Authors: M. Salvato, A. Giollo, M. Zen, M. Larosa, F. Frizzera, F. Arru, F. Vesentini, G. Bianchi, A. Doria
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Comorbidities are prevalent among people with rheumatoid arthritis (RA). Some authors have postulated that there is a tight relationship between comorbidities and refractoriness to treatments and a status of difficult-to-treat (DT2) RA. Nevertheless, strong evidence for this association is lacking. <h3>Objectives</h3> We compared the frequencies and type of comorbidities and extra-articular RA manifestations in a cohort of patients previously assessed for D2TRA. <h3>Methods</h3> This was a cross-sectional study in a multicentre cohort of patients diagnosed with RA between 2000 and 2019 and with a disease duration of more than two years (established disease). Participants were stratified according to their fulfillment of the EULAR definition of DT2RA. We analyzed comorbidities according to EULAR domains (cardiovascular diseases, malignancies, depression, osteoporosis, gastrointestinal diseases, and serious infections) plus the following not included in EULAR domains: fibromyalgia, thyroiditis, osteoarthritis, chronic kidney disease (CKD), and obesity. We compared the frequencies of each comorbidity by Chi-squared test between three groups: non-D2TRA, DT2RA 'persistent-inflammatory refractory RA' (PIRRA<sup>[1]</sup>) and DT2RA 'non-inflammatory refractory RA' (NIRRA<sup>[1]</sup>). DT2RA-PIRRA and DT2RA-NIRRA were defined according to the presence (PIRRA) or absence (NIRRA) of active inflammation as detected by raised inflammatory markers, clinical or ultrasound-proven synovitis. We also assessed extra-articular manifestations of RA (serositis, secondary Sjogren's syndrome, inflammatory eye diseases, neuropathy, interstitial lung disease, vasculitis, and rheumatoid nodules). Correlations were assessed by the Spearman test. P-values were not corrected for multiplicity due to the exploratory nature of this analysis. <h3>Results</h3> This cohort included 211 RA patients: D2TRA-PIRRA (n=32), DT2RA-NIRRA (n=34), non-D2TRA (n=145). At least one EULAR comorbidity was present in 46% of patients (range 0 to 4). The most represented EULAR comorbidities were cardiovascular diseases (29.5%), osteoporosis (19.5%) and gastrointestinal diseases (8.0%). The number of EULAR comorbidities was similar across groups (p=0.581 by Kruskal-Wallis test), and it was moderately correlated with age at RA onset (r=0.439, p&lt;0.0001). When separately analyzing each comorbidity, there were no significant differences yet a numerical increase in the prevalence of gastrointestinal diseases (15.6% vs 7.3% vs 0.0%, p=0.162) and serious infections (12.5% vs 6.0% vs 5.9%, p=0.328) in D2TRA-PIRRA compared to D2TRA-NIRRA and non-D2TRA patients (Figure 1A). With regard to comorbidities not encompassed in the EULAR domains, fibromyalgia was highly prevalent among D2TRA-NIRRA (23.5%) compared to DT2-RAPIRRA (3.1%) and non-D2TRA (2.7%) patients (p&lt;0.0001; Figure 1A). Extra-articular manifestations were recorded in 27.2% of non-DT2RA, 25.0% of DT2RA-PIRRA and 17.62% of DT2RA-NIRRA (p=0.787), without significant differences in single manifestations. DT2RA-PIRRA patients had numerically more serositis, inflammatory eye disease, and interstitial lung disease than non-D2TRA, while D2TRA-NIRRA patients only showed features of serositis and Sjogren's syndrome (Figure 1B). <h3>Conclusion</h3> Fibromyalgia was associated with D2TRA-NIRRA. Otherwise, we did not find a strong association between comorbidities or extra-articular manifestations and D2TRA. There were trends for more serious infections, gastrointestinal diseases and extra-articular manifestations in D2TRA-PIRRA. Our results suggest that the current definition of D2TRA may not adequately identify DT2RA patients with a substantial burden of comorbidities. <h3>Reference</h3> [1] Buch MH, Eyre S, McGonagle D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021 Jan;17(1):17-33. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Mariangela Salvato: None declared, Alessandro Giollo Consultant of: Galapagos, Novartis, Sandoz, Margherita Zen Consultant of: Astra Zeneca, Eli Lilly, Maddalena Larosa: None declared, Francesca Frizzera: None declared, Federico Arru: None declared, Filippo Vesentini: None declared, Gerolamo Bianchi: None declared, Andrea Doria Consultant of: GSK, Astra Zeneca, UCB.